We sought to examine stability associations between family history and variability of schizophrenia symptoms repeatedly examined during a naturalistic follow-up study. The Positive and Negative Syndrome Scale, the Insight and Treatment Attitudes Questionnaire, and the Abnormal Involuntary Movement Scale were administered to 69 patients with familial and 79 patients with sporadic schizophrenia, at hospital admission and at stabilization stage (about 16 months later). Analysis of covariance was applied to identify the association of symptom factors with familiality of schizophrenia. We found that schizophrenia patients with positive family histories had significantly higher dysphoric, activation and negative factors. However, familiality of activation and negative factors were dependent on additional variables such as age of onset (both factors), baseline ratings, insight, and side effects (negative factor). No significant association of family history with intensity of positive and autistic preoccupation factors was found. Familial schizophrenia is characterized by higher severity of dysphoric mood factors that may represent impaired emotional reactivity. It is suggested that dysphoric mood may be a useful phenotype for molecular genetic studies of schizophrenia with positive family history.